A breeding program has been carried out starting with two miniature pigs from different sources and selecting offspring according to tissue typing procedures aimed at defining the major histocompatibility complex of this species. By this procedure three herds of miniature swine, each homozygous for a different set of histocompatibility antigens at the MHC have been developed. MLC reactions, serologic typing, and skin graft survival times all indicate that these animals are homozygous for a major histocompatibility locus analogous to HL-A of man or H-2 of the mouse. Current projects include: 1) Assessment of survival of organs and tissue transplants among and between members of these herds as a model for tissue typing and transplantation; 2) purification and characterization of the major histocompatibility antigens of this species, and isolation and characterization of peptides from these antigens for sequence analyses and for assessment of immunologic reactivity, and 3) assessment of the immunologic parameters involved in tolerance to liver allografts in this species. Inbreeding in brother-sister fashion within each of these herds will be continued with the ultimate goal of establishing truly inbred animals if possible.